Attainment of Brown Adipocyte Features in White Adipocytes of Hormone-Sensitive Lipase Null Mice 英文参考文献.docVIP

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Attainment of Brown Adipocyte Features in White Adipocytes of Hormone-Sensitive Lipase Null Mice 英文参考文献.doc

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Attainment of Brown Adipocyte Features in White Adipocytes of Hormone-Sensitive Lipase Null Mice 英文参考文献

AttainmentofBrownAdipocyteFeaturesinWhite AdipocytesofHormone-SensitiveLipaseNullMice KristofferStro¨m1*,OlaHansson1¤,Ste′phanieLucas1,PernillaNevsten2,Ce′lineFernandez1,CeciliaKlint1, SofiaMove′rare-Skrtic3,FrankSundler1,ClaesOhlsson3,CeciliaHolm1 1Department of Experimental Medical Science, Lund University, Lund, Sweden, 2National Center for High Resolution Electron Microscopy, Lund University, Lund, Sweden,3ResearchCenterforEndocrinologyandMetabolism,TheSahlgrenskaAcademyatGothenburgUniversity,Gothenburg,Sweden Abstract Background:Hormone-sensitivelipase(HSL)isexpressedpredominantlyinadiposetissue,whereitplaysanimportantrole in catecholamine-stimulated hydrolysis of stored tri- and diglycerides, thus mobilizing fatty acids. HSL exhibits broad substratespecificityandbesidesacylglyceridesithydrolyzescholesterylesters,retinylestersandlipoidalesters.Despiteits roleinfattyacidmobilization,HSLnullmicehavebeenshowntoberesistanttodiet-inducedobesity. Methodology/Principal Findings: Following ahigh-fat diet (HFD) regimen, energy expenditure, measured using indirect calorimetry,wasincreasedinHSLnullmice.WhiteadiposetissueofHSLnullmicewascharacterizedbyreducedmassand reduced protein expression of PPARc, a key transcription factor in adipogenesis, and stearoyl-CoA desaturase 1, the expressionofwhichisknowntobepositivelycorrelatedtothedifferentiationstateoftheadipocyte.Theproteinexpression of uncoupling protein-1 (UCP-1), the highly specific marker of brown adipocytes, was increased 7-fold in white adipose tissueofHSLnullmicecomparedtowildtypelittermates.Transmissionelectronmicroscopyrevealedanincreaseinthesize ofmitochondriaofwhiteadipocytesofHSLnullmice.ThemRNAexpressionofpRbandRIP140wasdecreasedinisolated whiteadipocytes,whiletheexpressionofUCP-1andCPT1wasincreasedinHSLnullmicecomparedtowildtypelittermates. Basaloxygenconsumptionwasincreasedalmost3-foldinwhiteadiposetissueofHSLnullmiceandwasaccompaniedby increaseduncouplingactivity. Conclusions: These data suggest that H